Viedma ripening is the attrition-induced spontaneous chiral amplification of a conglomerate crystal mixture. To demonstrate the general nature of this deracemization process, we have extended attrition-enhanced chiral amplification to 10 achiral organic molecules that form conglomerate chiral crystals: benzil (1), diphenyl disulfide (2), benzophenone (3), tetraphenylethylene (4), guanidine carbonate (5), butylated hydroxytoluene (6), hippuric acid (7), ninhydrin (8), cytosine (9), and adeninium dinitrate (10). In these experiments the time required to reach homochirality was as low as 3 h and typically ranged from 25 to 50 h. In most cases amplification to homochirality of both enantiomers was observed in repeat experiments, although often in a nonstochastic fashion, reflecting the scalemic nature of the starting material. We have also demonstrated the utility of quantitative circular dichroism (CD) to determine enantiomeric excess in systems where chirality exists only in the solid-state.

Sphingolipids, in particular ceramides, play vital role in pathophysiological processes linked to metabolic syndrome, with implications in the development of insulin resistance, pancreatic ß-cell dysfunction, type 2 diabetes, atherosclerosis, inflammation, nonalcoholic steatohepatitis, and cancer. Ceramides are produced by the hydrolysis of sphingomyelin, catalyzed by different sphingomyelinases, including neutral sphingomyelinase 2 (nSMase2), whose dysregulation appears to underlie many of the inflammation-related pathologies. In this review, we discuss the current knowledge on the biochemistry of nSMase2 and ceramide production and its regulation by inflammatory cytokines, with particular reference to cardiometabolic diseases. nSMase2 contribution to pathogenic processes appears to involve cyclical feedforward interaction with proinflammatory cytokines, such as TNF-α and IL-1ß, which activate nSMase2 and the production of ceramides, that in turn triggers the synthesis and release of inflammatory cytokines. We elaborate these pathogenic interactions at the molecular level and discuss the potential therapeutic benefits of inhibiting nSMase2 against inflammation-driven cardiometabolic diseases.

Many drugs can cause unexpected muscle disorders, often necessitating the cessation of an effective medication. Inhibition of monocarboxylate transporters (MCTs) may potentially lead to perturbation of l-lactic acid homeostasis and muscular toxicity. Previous studies have shown that statins and loratadine have the potential to inhibit l-lactic acid efflux by MCTs (MCT1 and 4). The main objective of this study was to confirm the inhibitory potentials of atorvastatin, simvastatin (acid and lactone forms), rosuvastatin, and loratadine on l-lactic acid transport using primary human skeletal muscle cells (SkMC). Loratadine (IC50 31 and 15 µM) and atorvastatin (IC50 ~130 and 210 µM) demonstrated the greatest potency for inhibition of l-lactic acid efflux at pH 7.0 and 7.4, respectively (~2.5-fold l-lactic acid intracellular accumulation). Simvastatin acid exhibited weak inhibitory potency on l-lactic acid efflux with an intracellular lactic acid increase of 25–35%. No l-lactic acid efflux inhibition was observed for simvastatin lactone or rosuvastatin. Pretreatment studies showed no change in inhibitory potential and did not affect lactic acid transport for all tested drugs. In conclusion, we have demonstrated that loratadine and atorvastatin can inhibit the efflux transport of l-lactic acid in SkMC. Inhibition of l-lactic acid efflux may cause an accumulation of intracellular l-lactic acid leading to the reported drug-induced myotoxicity.